Urinary assays for desmosine and hydroxylysylpyridinoline in the detection of cirrhosis.
OBJECTIVE
Non-invasive markers of liver fibrosis have great potential for both the diagnosis and therapy of liver disease and cirrhosis. The aim of this study was to evaluate the potential of urinary amino acids desmosine (DES) and isodesmosine (IDES) derived from the breakdown of elastin and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) derived from fibrillar collagen in diagnosing chronic liver disease.


METHODS
We studied 48 patients with chronic liver disease who had varying degrees of liver fibrosis, graded 0-6 using a modified Knodell score, and 20 control subjects without liver disease. Urinary DES (microg/g creatinine) and HP (nmol/mmol creatinine) were measured by an isotope dilution, high performance liquid chromatography method. For liver disease patients, aminoterminal propeptide of type III procollagen (PIIINP) and alanine aminotransferase were determined. The urine and serum markers were correlated to degree of fibrosis and inflammation on liver biopsies. Differences between groups were analyzed by ANOVA and multiple linear regression was applied to determine independence of variables. Sensitivity, specificity and receiver operating curves were derived for each marker.


RESULTS
In the 17 patients with liver fibrosis score of 5-6, mean urinary DES, IDES, HP and LP were all significantly greater than in the control group (p<0.05). Urinary DES and IDES correlated best with fibrosis score, r=0.61 for both markers. The correlation coefficient between serum PIIINP and fibrosis score was 0.47. Urinary DES and HP each had an overall diagnostic accuracy of 77% for fibrosis. Combining markers improved accuracy to over 80%. No correlation was seen between the urinary markers and inflammation scores.


CONCLUSIONS
Urinary DES and HP are potentially useful clinical markers for liver fibrosis, especially when used in combination or in association with PIIINP.
Afdhal
N H
NH
Evans Department of Medicine, Boston Medical Center and Boston University School of Medicine, 02118, USA.
Keaveny
A P
AP
Cohen
S B
SB
Nunes
D P
DP
Maldonado
N
N
O'Brien
M
M
Stone
P J
PJ
D000328:Adult; D000596:Amino Acids / Q000652:urine*; D003895:Desmosine / Q000652:urine*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000652:urine; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood
D000596:Amino Acids; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D003895:Desmosine; C015484:pyridinoline